Biological markers demonstrate utility and predictive value in inflammatory bowel disease
Biological markers (“biomarkers”) may have applications in inflammatory bowel disease (IBD), a chronic disease of the gastrointestinal tract. Clinicians are presented with several challenges when treating IBD. Instead of performing expensive and invasive endoscopic procedures - if even possible, as resources for these procedures can be limited - biomarkers could be used to diagnose, assess disease activity and prognosis, and guide medical therapy, particularly in situations where novel biologics are involved. At this time, the use of biomarkers is limited, since few have been useful in predicting disease severity, prognosis and therapeutic response in IBD. Previous research cohorts studying biomarkers are limited due to varying heterogeneity between subjects that confounds the results since patients have variable disease courses. The main aim of this work was to evaluate the utility of biomarkers in IBD. To do this, biomarkers were included into a composite score with other patient reported outcomes (PRO) to predict endoscopic disease activity. Next, we examined the role of biomarkers in newly diagnosed IBD. Lastly, fecal calprotectin (FC) was evaluated in healthy pregnant and IBD patients, establishing reference values and practicality in this clinical group. We also studied the relationship between biomarkers and environmental factors, such as fecal microbiota. We hypothesized biomarker concentration would be elevated with increased clinical and endoscopic measures, and predictive of response to medical therapy in newly diagnosed patients. Additionally, we theorized the inclusion of biomarkers into composite scores would outperform existing scoring models in predicting endoscopic severity. Furthermore, FC levels would be below the limit of detection in healthy pregnancy and elevated in IBD pregnancy. The inclusion of biomarkers into composite scoring models outperformed existing clinical scores. In newly diagnosed patients, modest relationships were found between biomarkers and clinical and endoscopic markers of disease. Lastly, the presence of FC was elevated in pregnant IBD and not significant in healthy pregnancy; thus, FC is useful in IBD and pregnancy. Our work confirmed the significance of biomarkers in several clinical areas of IBD, along with the issues presented in recruiting newly diagnosed patients in small research centres. Future work will incorporate biomarkers into medical triage and as an endpoint in nutritional interventions.
DegreeDoctor of Philosophy (Ph.D.)
SupervisorZello, Gordon A.; Jones, Jennifer L.
CommitteeAlcorn, Jane; Fowler, Sharyle A.; Rodgers, Carol; Dahl, Wendy
Copyright DateDecember 2015